McKernan Patrick, Virani Needa A, Faria Gabriela N F, Karch Clément G, Prada Silvy Ricardo, Resasco Daniel E, Thompson Linda F, Harrison Roger G
Department of Neurology, Neurosurgery, and Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, and Dana-Farber Cancer Institute, Boston, MA, USA.
Nanoscale Res Lett. 2021 Jan 7;16(1):9. doi: 10.1186/s11671-020-03459-x.
The greatest contributors to cancer mortality are metastasis and the consequences of its treatment. Here, we present a novel treatment of metastatic breast cancer that combines photothermal therapy with targeted single-walled carbon nanotubes (SWCNTs) and immunostimulation with a checkpoint inhibitor. We find that the selective near-infrared photothermal ablation of primary orthotopic EMT6 breast tumors in syngeneic BALB/cJ mice using an annexin A5 (ANXA5) functionalized SWCNT bioconjugate synergistically enhances an anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4)-dependent abscopal response, resulting in an increased survival (55%) at 100 days after tumor inoculation. In comparison, there was no survival at 100 days for either photothermal therapy by itself or immunostimulation by itself. Prior to photothermal therapy, the SWCNT-ANXA5 bioconjugate was administered systemically at a relatively low dose of 1.2 mg/kg, where it then accumulated in tumor vasculature via ANXA5-dependent binding. During photothermal therapy, the average maximum temperature in the tumor reached 54 °C (duration 175 s). The mechanism of prolonged survival resulting from combinatorial photothermal ablation and immune stimulation was evaluated by flow cytometric quantification of splenic antitumoral immune effector cells and serum cytokine quantification.
癌症死亡率的最大贡献因素是转移及其治疗后果。在此，我们提出了一种转移性乳腺癌的新疗法，该疗法将光热疗法与靶向单壁碳纳米管（SWCNT）相结合，并与检查点抑制剂进行免疫刺激。我们发现，使用膜联蛋白A5（ANXA5）功能化的SWCNT生物共轭物对同基因BALB/cJ小鼠原发性原位EMT6乳腺肿瘤进行选择性近红外光热消融，可协同增强抗细胞毒性T淋巴细胞相关蛋白4（抗CTLA-4）依赖性远隔效应，导致肿瘤接种后100天时生存率提高（55%）。相比之下，单独的光热疗法或单独的免疫刺激在100天时均无生存。在光热疗法之前，以相对低剂量1.2 mg/kg全身给药SWCNT-ANXA5生物共轭物，其随后通过ANXA5依赖性结合在肿瘤血管中积累。在光热疗法期间，肿瘤内的平均最高温度达到54°C（持续时间175秒）。通过流式细胞术定量脾脏抗肿瘤免疫效应细胞和血清细胞因子定量，评估了联合光热消融和免疫刺激导致长期生存的机制。
